Note: Pycnogenol® is a patented nutrient supplement extracted from the bark of the European coastal pine Pinus maritima. Pycnogenol® consists of flavonoids, catechins, procyanidins, and phenolic acids, which are the same constituents found in grape seed, but not the same supplement. For more information on Pycnogenol®, see the individual monograph.

Wine is a fermented grape product and is discussed in more detail in a separate monograph.

The focus of this monograph is all parts of the plant Vitis vinifera, and other species of grape are not specifically discussed. However, in many cases, the species of grape is unclear.

The focus of this monograph is all parts of the plant Vitis vinifera. Specific information on resveratrol may be found in a separate bottom line.

Grape leaves, sap, seed, and fruit have been used medicinally since the Greek empire. Different parts of the plant have been used traditionally for conditions such as skin and eye irritation, bleeding, varicose veins, diarrhea, cancer, and smallpox.

Interest in grape products increased with the recognition of the potential heart-protective effects of wine consumption in French men consuming a high-fat diet. Grape has been shown to possess antioxidant, blood clot-preventing, and cholesterol-lowering properties.

The antioxidant properties of grape seed oligomeric proanthocyanidins (OPCs) make these extracts potential therapies for many diseases. Research has documented the effectiveness of grape seed OPCs for damaged blood vessel valves or weak blood vessels, diabetic retinopathy (eye damage), edema (fluid accumulation) in the arms and legs, and high cholesterol. OPCs appear to be well tolerated, with few side effects noted in the available research. However, long-term studies assessing safety are lacking.

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

GRADE *

High-quality research reports that that grape seed OPCs may reduce the symptoms of poor circulation in leg veins. Furthermore, red leaf vine extract may be effective for preventing and managing chronic venous insufficiency.

A

Research shows that grape seed ingredients may speed the reduction of swelling after injury, including surgery. Larger, high quality studies are needed to confirm these results.

A

Diabetic retinopathy is a disease of the small blood vessels in the eye's retina. Early research using OPCs and the brand name product Endotelon® has shown beneficial effects in stopping disease progression. Additional research is needed in this area.

B

Early research suggests that ingredients from grape seed may make small blood vessels less fragile. Additional research is needed in this area.

B

Grape seed oil is a popular carrier oil used in aromatherapy. There is mixed evidence as to whether aromatherapy may benefit agitation in dementia. Additional research is needed in this area.

C

Studies have found grape and grape products to contain antioxidants. Antioxidants may protect against heart disease. Additional research is needed in this area.

C

Early research suggests grape extract may increase power in athletes. Additional research is needed in this area.

C

Grape lacks supportive evidence for improving nausea and vomiting from chemotherapy. Additional research is needed in this area.

C

Early research suggests grape juice may benefit blood flow. More high-quality studies are needed to draw a conclusion.

C

Early research suggests that grape may benefit blood pressure, cholesterol, and blood flow. Additional research is needed in this area.

C

Grape extract may have a beneficial effect on blood pressure and heart rate. Additional research is needed in this area.

C

Early research suggests OPCs may reduce LDL ("bad") cholesterol. Grape may also possess antioxidant properties and reduce clogged arteries. Additional research is needed in this area.

C

Grape juice may increase the number of immune system cells. Additional research is needed in this area.

C

Grape seed extract may improve some symptoms of liver disease. Additional research is needed in this area.

C

Melasma is a skin discoloration that may occur due to hormonal imbalances. Antioxidants are thought to improve skin color, and grape seed extract is thought to have antioxidant activity. Additional research is needed in this area.

C

Grape juice may benefit verbal learning and memory in the elderly. Additional research is needed in this area.

C

Grape seed may reduce stomach pain associated with an inflamed pancreas. Additional research is needed in this area.

C

Early research shows positive results on grape seed for PMS symptoms. Additional research is needed in this area.

C

Grape seed contains OPCs, which may have antioxidant properties. Antioxidants have potential radioprotective properties. Although initial results show a lack of benefit, larger studies are needed.

C

Epicatechin is an antioxidant component of grape seed extract, which has become increasingly popular in skin products. Combination products that include grape seed extract have shown promising effects. Additional research is needed in this area.

C

Grape may improve sensitivity to light and glare. Additional research is needed in this area.

C

Early research suggests that grape juice may reduce waist circumference. Additional research is needed in this area.

C

Grape seed has been used to treat immune system disorders due to its antioxidant effects. However, research on grape seed's effect on allergies shows mixed results. Additional research is needed in this area.

D

* Key to grades

A: Strong scientific evidence for this useB: Good scientific evidence for this useC: Unclear scientific evidence for this useD: Fair scientific evidence for this use (it may not work)F: Strong scientific evidence against this use (it likley does not work)

Tradition / Theory
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

For allergies, grape seed extract has been taken at a dose of 100 milligrams by mouth twice daily for unspecified duration.

As an antioxidant, 100-480 milliliters of Concord, purple, or red grape juice has been taken by mouth daily for 1-12 weeks. A standardized grape product (100 milliliters, one dose equivalent to 1.25 cups of fresh grapes) has been taken by mouth once or twice daily for 21 days. Extracts of grape, grape seed, or grape skin (200-400 milligrams) have been taken as capsules or tablets 1-3 times daily for up to 12 weeks. A single dose of one gram per kilogram of dried black grape per kilogram has been taken by mouth. A 46 gram dose of freeze-dried grape powder has been taken by mouth for four weeks.

For athletic performance, 400-milligram capsules of grape extract have been taken by mouth once daily for one month.

For chemotherapy side effects, four ounces of Concord grape juice has been taken by mouth daily before meals for one week.

For chronic venous insufficiency (damaged vein valves), tablets containing 360-720 milligrams of red vine leaf extract AS 195 have been taken by mouth daily for 6-12 weeks. Endotelon® (150-300 milligrams) and oligomeric proanthocyanidins (300 milligrams) have been taken by mouth daily for 1-3 months.

For coronary artery disease, 4-8 milliliters of purple grape juice per kilogram has been taken once or twice by mouth daily for 14-28 days.

For diabetic retinopathy, Endotelon® (100-200 milligrams) has been taken by mouth daily for several weeks to three months. Grape seed proanthocyanidins (100 milligrams) have been taken by mouth daily for one year.

For edema (swelling), Endotelon® (200-400 milligrams) and oligomeric proanthocyanidins (OPCs) (300 milligrams) have been taken by mouth for 30 days to six months. A dose of 300 milligrams of Endotelon® has been taken daily five days prior to cosmetic surgery and on postoperative days 2-6.

For heart disease prevention, 100-500 milliliters of Concord and red grape juice has been consumed daily for up to 12 weeks. Grape extract tablets (300 or 350 milligram tablets) have been taken once or twice daily for up to one year. Grape powder (36 grams), standardized grape product (each dose equivalent to 1.25 cups of fresh grapes), wine grape solids (1,500 milligrams), grape seed (800 milligrams), and grape antioxidant dietary fiber (7.5 grams) have been taken once or twice daily for up to 16 weeks. Doses of 150-2,000 milligrams of grape seed extract have been taken by mouth for 2-24 weeks.

For high blood pressure, 150-2,000 milligrams of grape seed extract have been taken by mouth for 2-24 weeks. Concord grape juice, consumed at 5.5-7milliliters per kilogram daily for eight weeks, has been taken. Grape seed polyphenols have been taken at a dose of 1,000 milligrams daily for six weeks. Additionally, 46 grams of freeze-dried whole grape powder has been taken by mouth daily for 4 weeks.

For high cholesterol, grape antioxidant dietary fiber (7.7 grams) and grape seed extract (100-400 milligrams) have been taken once or twice daily by mouth for two months to sixteen weeks.

For immune function, 360 milliliters of Concord grape juice has been consumed daily for nine weeks.

For liver disease, 1,000 milligrams of grape extract has been taken twice daily for three months.

For melasma (dark skin spots), grape seed extract at an unknown dose has been taken by mouth for six months.

For memory, 6-9 milliliters of Concord grape juice per kilogram has been consumed by mouth for 12 weeks.

For pancreatitis (inflamed pancreas), 100 milligrams of grape seed proanthocyanidin extract (GSPE) (ActiVin®) has been taken by mouth 2-3 times daily.

For radiation injuries, 100 milligrams of GSPE has been taken by mouth three times daily for six months. A dose of 100 milligrams of grape procyanidins has been taken daily by mouth for 60 days.

For skin aging, two tablets of a combination product containing grape seed extract (Imedeen® Prime Renewal®) has been taken twice daily for six months.

For vascular fragility, 150 milligrams of grape seed extract (GSE) has been taken by mouth twice daily for eight weeks. A dose of 150 milligrams of procyanidolic oligomers has been taken by mouth daily for 28 days. Additionally, 100 milligrams of Endotelon® has been taken by mouth daily for at least one month.

For vision problems, Endotelon® has been taken at a dose of 200 milligrams daily for five weeks.

For weight loss, 480 milliliters of Concord grape juice has been consumed daily for 12 weeks.

Children (younger than 18 years)

There is no proven safe and effective dose of grape seed or OPCs in children.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid with known allergy or sensitivity to grape (Vitis spp.), any of its constituents, or other members of the Vitaceae family.

Cases of allergic reactions to grape, grape products, oligomeric proanthocyanidins (OPCs), grape skin extract, or grape color extract have been reported. Cases of anaphylactic shock after consumption of grapes or grape products have been reported. Crossover allergies to apples, bananas, cherries, and peaches have been reported. Occupational allergies to grape pollen have been reported.

Side Effects and Warnings

Grape and grape products are likely safe when consumed by people without a grape allergy in amounts naturally found in foods. Grape and grape products are likely safe when used by healthy adults in suggested doses for medical purposes.

Grape may lower blood sugar levels. Caution is advised in people with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Grape may increase the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

Use cautiously in people taking agents metabolized by cytochrome P450 enzymes, agents that prevent blood clots such as warfarin, aspirin, nonsteroidal anti-inflammatory drugs, or agents that prevent platelet aggregation. Use cautiously in people on methotrexate therapy or in combination with vitamin C.

Note: Discontinue use of grape products or grape parts, at levels greater than those commonly found in the diet, at least two weeks prior to surgery or a dental procedure, in order to prevent bleeding.

Note: Wash grapes well before eating to remove pesticide residues. According to secondary sources, grapes are on a list of the top 12 fruits and vegetables to buy organic.

Pregnancy and Breastfeeding

Use grape seed extract cautiously in amounts greater than those normally found in food, due to the lack of efficacy and safety information.

Resveratrol, a chemical found in grape, may increase calcium levels and induce uterine contractions

There is a lack of scientific evidence on the use of grape during pregnancy or lactation.

Grape may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

Grape may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

Grape may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may be decreased in the blood, and the intended effects may be reduced. People taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

Grape may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Grape may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Grape may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too low in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.

Grape may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.

Because grape contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties may be altered.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.